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Metformin enhances ...
Metformin enhances LDL-cholesterol uptake by suppressing the expression of the pro-protein convertase subtilisin/kexin type 9 (PCSK9) in liver cells
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- Ali, A. (author)
- University of Sharjah
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- Unnikannan, H. (author)
- University of Sharjah
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- Shafarin, J. (author)
- University of Sharjah
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- Bajbouj, K. (author)
- University of Sharjah
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- Taneera, J. (author)
- University of Sharjah
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- Muhammad, J. S. (author)
- University of Sharjah
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- Hasan, H. (author)
- University of Sharjah
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- Salehi, Albert (author)
- University of Gothenburg,Lund University,Lunds universitet,Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology,Öcellsfysiologi,Forskargrupper vid Lunds universitet,Islet cell physiology,Lund University Research Groups
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- Awadallah, S. (author)
- University of Sharjah
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Hamad, M. (author)
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(creator_code:org_t)
- 2022-03-02
- 2022
- English.
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In: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 76, s. 543-557
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http://dx.doi.org/10...
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Abstract
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- Purpose: Metformin (MF) intake associates with reduced levels of circulating low-density lipoprotein-cholesterol (LDL-C). This has been attributed to the activation of AMPK, which differentially regulates the expression of multiple genes involved in cholesterol synthesis and trafficking. However, the exact mechanism underlying the LDL-C lowering effect of MF remains ambiguous. Methods: MF-treated Hep-G2 and HuH7 cells were evaluated for cell viability and the expression status of key lipid metabolism-related genes along with LDL-C uptake efficiency. Results: MF treatment resulted in decreased expression and secretion of PCSK9, increased expression of LDLR and enhanced LDL-C uptake in hepatocytes. It also resulted in increased expression of activated AMPK (p-AMPK) and decreased expression of SREBP2 and HNF-1α proteins. Transcriptomic analysis of MF-treated Hep-G2 cells confirmed these findings and showed that other key lipid metabolism-related genes including those that encode apolipoproteins (APOB, APOC2, APOC3 and APOE), MTTP and LIPC are downregulated. Lastly, MF treatment associated with reduced HMG-CoA reductase expression and activity. Conclusions: These findings suggest that MF treatment reduces circulating LDL-C levels by suppressing PCSK9 expression and enhancing LDLR expression; hence the potential therapeutic utility of MF in hypercholesterolemia.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- HNF-1α
- LDL-cholesterol
- LDLR
- Metformin
- PCSK9
- SREBP2
Publication and Content Type
- ref (subject category)
- art (subject category)
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Endocrine
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To the university's database
- By the author/editor
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Ali, A.
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Unnikannan, H.
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Shafarin, J.
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Bajbouj, K.
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Taneera, J.
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Muhammad, J. S.
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show more...
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Hasan, H.
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Salehi, Albert
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Awadallah, S.
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Hamad, M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
- Articles in the publication
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Endocrine
- By the university
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University of Gothenburg
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Lund University